WO2024076173A1 - Composition pour induire une différenciation de cellules souches issues du tissu adipeux en cellules de papille dermique, et procédé de différenciation utilisant la composition - Google Patents
Composition pour induire une différenciation de cellules souches issues du tissu adipeux en cellules de papille dermique, et procédé de différenciation utilisant la composition Download PDFInfo
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- WO2024076173A1 WO2024076173A1 PCT/KR2023/015333 KR2023015333W WO2024076173A1 WO 2024076173 A1 WO2024076173 A1 WO 2024076173A1 KR 2023015333 W KR2023015333 W KR 2023015333W WO 2024076173 A1 WO2024076173 A1 WO 2024076173A1
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- cells
- dermal papilla
- composition
- adipose
- derived stem
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
Definitions
- the present invention relates to a composition for inducing differentiation of adipose-derived stem cells into dermal papilla cells and a differentiation method using the composition.
- a typical human's hair goes through a cycle of hair growth and hair loss, repeating the growth phase (anagen) when the hair actively grows, the catagen phase (catagen) when the hair begins to deteriorate, and the resting phase (telogen) when the hair stops growing or goes into rest.
- Hair loss is broadly classified into natural hair loss, in which growing hair naturally falls out of the hair follicle through a normal growth cycle, and abnormal hair loss, which occurs due to genetic factors, abnormal hormonal secretion, mental stress, disease, and drug side effects.
- Dermal papilla cells are a type of dermal fibroblast cell located in the dermal papilla at the bottom of the hair follicle.
- Capillaries are distributed in the dermal papilla cells, which supply oxygen and nutrients to the hair follicle and IGF-1 (insulinlike growth factor).
- growth factors such as fator-1), KGF (keratinocyte growth factor), ⁇ -FGF ( ⁇ -fibroblast growth factor), HGF (hepatocyte growth factor), SCF (stem cell factor), and VEGF (vascular endothelial growth factor) It regulates the growth of hair follicle epithelial cells by secreting inhibition factors such as epidermal growth factor (EGF) and transforming growth factor- ⁇ (TGF- ⁇ ).
- EGF epidermal growth factor
- TGF- ⁇ transforming growth factor- ⁇
- the present invention discloses a technology for differentiating human adipose tissue-derived mesenchymal stem cells into dermal papilla cells.
- the purpose of the present invention is to provide a composition for inducing differentiation of adipose-derived stem cells into dermal papilla cells.
- Another object of the present invention is to provide a method for differentiating adipose-derived stem cells into dermal papilla cells using the composition.
- the present invention allows Morroniside to be treated with human adipose-derived stem cells together with factors such as bFGF (Fibroblast Growth Factor-basic) and BMP2 (Bone morphogenetic protein 2). Then, from the stem cells, dermal papilla cells that show similar characteristics in terms of expression of essential genes of dermal papilla cells and commercially sold dermal papilla cells (PromoCell, Human Centered Science, Germany) used as control cells are induced to differentiate, and the differentiation is induced.
- factors such as bFGF (Fibroblast Growth Factor-basic) and BMP2 (Bone morphogenetic protein 2).
- the present invention is provided based on the results of these experiments.
- the present invention is for inducing differentiation of fat-derived (i.e. isolated from human adipose tissue) stem cells containing moroniside as an active ingredient into dermal papilla cells. It can be identified by composition.
- moroniside acts alone or together with an inactive carrier component as an active ingredient that induces differentiation of human adipose-derived stem cells into dermal papilla cells.
- the IUPAC name of moroniside is ⁇ methyl (1S,3R,4aS,8S,8aS)-3-hydroxy-1-methyl-8-[(2S,3R,4S,5S,6R)-3,4,5- It is a known compound called ‘trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-1,3,4,4a,8,8a-hexahydropyrano[3,4-c]pyran-5-carboxylate’ and its CAS number is 25406. It is -64-8, and is a substance known to regulate hair growth through the Wnt/ ⁇ -catenin signaling pathway (Scientific Reports, (2016) 8:13785).
- composition of the present invention may additionally contain bFGF (Fibroblast Growth Factor-basic) and/or BMP2 (Bone morphogenetic protein 2) to complement or increase the differentiation inducing activity of moroniside.
- bFGF Fibroblast Growth Factor-basic
- BMP2 Ben morphogenetic protein 2
- these factors may be of human origin (meaning that they are isolated from human blood, etc., or manufactured by genetic recombination, and the amino acid sequence is the same as that of humans).
- composition of the present invention may contain the active ingredient moroniside in the amount necessary to sufficiently differentiate adipose-derived stem cells into dermal papilla cells or to the intended degree. Typically, it will be included in the range of 3 to 20 ⁇ M, especially 5 to 15 ⁇ M.
- composition of the present invention contains bFGF and/or BMP2, in order to differentiate into dermal papilla cells sufficiently or to the intended extent, bFGF is contained in the range of 3 to 20 ng/ml and BMP2 is contained in the range of 0.3 to 3 ng/ml. It would be desirable.
- composition of the present invention may include a solvent in addition to the active ingredient moroniside.
- solvent may be cell culture medium, buffer, isotonic solution, or other suitable solvent such as purified water or dimethyl sulfoxide (DMSO).
- the cell culture medium in the present invention is not particularly limited and any basic medium used in the art for culturing mammalian cells can be used.
- the basic medium is for cell growth, proliferation and/or amplification, and basically contains sugars, amino acids, mineral salts, and may optionally contain vitamins, trace elements, antimicrobial agents, growth factors, hormones, buffers, isotonic agents, etc. You can.
- Saccharides may be monosaccharides, disaccharides, etc., and specifically include glucose, fructose, mannose, galactose, ribose, sorbose, ribulose, lactose, maltose, sucrose, raffinose, or mixtures of one or more of these. can be used
- Amino acids included in the basic medium are aspartic acid, glutamic acid, asparagine, serine, glutamine, histidine, glycine, threonine, arginine, alanine, tyrosine, cysteine, valine, methionine, norvaline, tryptophan, phenylalanine, isoleucine, leucine, and lysine. , hydroxyproline, sarcosine and/or proline.
- the amino acid is preferably a synthetic amino acid, and such synthetic amino acid may be in the form of a dipeptide or tripeptide. These dipeptides and tripeptides can be converted to free amino acids in cell cultures containing cells.
- the basic medium contains inorganic salts such as sodium chloride, potassium chloride, calcium chloride, magnesium sulfate, and sodium dihydrogen phosphate, which help maintain osmotic balance and regulate membrane potential by providing sodium, potassium, and calcium ions. Additional items may be included.
- the basic medium may optionally contain vitamins. Many vitamins are essential for cell growth and proliferation and cannot be synthesized in sufficient amounts by cells, so they need to be sufficiently supplemented in cell culture media. Vitamins such as vitamin A, B vitamins, vitamin C, and vitamin E may be included in the basic medium. In particular, B vitamins such as thiamine, riboflavin, pyridoxine, cyanocobalamin, biotin, folic acid, pantothenic acid, and nicotinamide are preferably added to promote cell growth.
- the basic medium may optionally contain trace elements, antibiotics, growth factors, hormones, buffers, isotonic agents, etc. in addition to sugars, amino acids, and vitamins.
- Trace elements may be added to the basic medium for proper cell growth and to maintain enzyme function.
- Examples of such trace elements include copper, zinc, selenium, and tricarboxylic acid intermediates.
- Antimicrobial agents can be added to the basic medium to prevent contamination by external microorganisms, specifically antibiotics such as penicillin, streptomycin, and fungizone, antifungal agents such as amphotericin B, Mycoplasma inhibitors such as gentamicin, ciprofloxacin, azithromycin, and tylosin may be used.
- antibiotics such as penicillin, streptomycin, and fungizone
- antifungal agents such as amphotericin B, Mycoplasma inhibitors such as gentamicin, ciprofloxacin, azithromycin, and tylosin may be used.
- Growth factors can be added to the basic medium for cell proliferation.
- growth factors include epidermal growth factor (EGF), fibroblast growth factor (FGF), and insulin-like growth factor (insulin-like growth factor).
- IGF insulin-like growth factor
- nerve growth factor NGF
- PDGF platelet-derived growth factor
- TGF vascular endothelial growth factor
- VEGF vascular endothelial growth factor growth factor
- activin A activin A, etc.
- hormones that can be added to the basic medium include insulin, hydrocortisone, triiodothyronine, estrogen, androgen, progesterone, prolactin, follicle-stimulating hormone, gastrin-releasing peptide, dexamethasone, estradiol, and glucagon.
- the basic medium contains buffering agents such as citrate, phosphate, succinate, tartrate, fumarate, gluconate, oxalate, lactate, acetate, histidine, and tris, or sodium chloride, potassium chloride, boric acid, sodium borate, mannitol, and glycerin. , propylene glycol, polyethylene, glycol, maltose, sucrose, erythritol, arabitol, xylitol, sorbitol trihalose, glucose, etc. may be included.
- buffering agents such as citrate, phosphate, succinate, tartrate, fumarate, gluconate, oxalate, lactate, acetate, histidine, and tris, or sodium chloride, potassium chloride, boric acid, sodium borate, mannitol, and glycerin.
- propylene glycol polyethylene, glycol, maltose, sucrose, erythritol, arabitol
- the basic medium contains cell adhesion factors such as type 1 or 2 collagen, gelatin, fibronectin, laminin, poly-L-lysine, and poly-D-lysine, as well as salt, free fatty acids, hormones, and vitamins that bind to tissue and Albumin, which transports between cells and plays a role in regulating pH and osmotic pressure, and transferrin, which plays an important role in iron transport, may be additionally included.
- cell adhesion factors such as type 1 or 2 collagen, gelatin, fibronectin, laminin, poly-L-lysine, and poly-D-lysine
- salt free fatty acids
- hormones hormones
- transferrin which plays an important role in iron transport
- DMEM Dulbecco's Modified Eagle's Medium
- MEM Minimal Essential Medium
- BME Base Medium Eagle
- RPMI 1640 F-10, F-12, DMEM/F12, MEM- ⁇ (Minimal Essential Medium- ⁇ ), G-MEM (Glasgow's Minimal Essential Medium), IMDM (Iscove's Modified Dulbecco's Medium), MacCoy's 5A medium, AmnioMax complete medium, AminoMaxII complete medium, EBM (Endothelial Basal Medium) medium, Chang's Medium, MesenCult-XF, DMEM/HG (Dulbecco's Modified Eagle's Medium high glucose) medium, and MCDB+DMEM/LG (MCDB +Dulbecco's Modified Eagle's Medium low glucose) medium. You can.
- the solvent included in the composition of the present invention may be a buffer solution, which includes citrate, phosphate, succinate, tartrate, fumarate, gluconate, oxalate, lactate, acetate, histidine, tris, etc. It may be a physiological saline solution. In particular, it may be phosphate buffered saline (PBS), Tris Buffered Saline (TBS), HEPES Buffered Saline, DPBS (Dulbecco's phosphate-buffered saline), etc.
- PBS phosphate buffered saline
- TBS Tris Buffered Saline
- HEPES Buffered Saline HEPES Buffered Saline
- DPBS Dulbecco's phosphate-buffered saline
- Solvents included in the composition of the present invention may also include sodium chloride, potassium chloride, boric acid, sodium borate, mannitol, glycerin, propylene glycol, polyethylene, glycol, maltose, sucrose, erythritol, arabitol, xylitol, sorbitol trihalose, glucose. It may be an isotonic solution containing such as an isotonic agent. This isotonic solution may be Ringer's solution, lactate Ringer's solution, acetic acid Ringer's solution, bicarbonate Ringer's solution, or 5% glucose aqueous solution, and can be prepared and used directly or purchased commercially.
- the adipose-derived stem cells (ADSC) of the present invention have self-renewal ability and can differentiate into cells of various types such as skin, cartilage, and bone, as well as bone marrow-derived stem cells or umbilical cord blood-derived stem cells. Compared to stem cells, it is easier to collect and can be cultured in large quantities, and because it contains a large amount of stem cells, it is highly utilized in cell therapy products.
- adipose-derived stem cells have self-renewal and differentiation abilities, their origin is not particularly limited and may be derived from humans, monkeys, pigs, horses, cows, sheep, dogs, cats, mice, or rabbits. Preferably it is of human origin.
- the present invention relates to a method for producing dermal papilla cells differentiated from adipose-derived stem cells, comprising the step of treating and culturing the composition for inducing differentiation of the present invention as described above in the adipose-derived stem cell culture medium. will be.
- the culture temperature may be in the range of 25-40°C, preferably 35 ⁇ 2°C.
- culture is performed until differentiation into dermal papilla cells is sufficient or achieved as intended.
- culturing can be performed for a period of 24 hours, 48 hours, 72 hours, 96 hours, 5 days, 6 days, 7 days, 8 days, 9 days, or more.
- the amount of carbon dioxide (CO 2 ) is 10% to 1% (v/v), preferably 8% to 2% (v/v). ), especially at 5% (v/v).
- the culture can be performed in a closed incubator, especially in a closed incubator in which a sterile state is maintained.
- Incubators suitable for the present invention include GE Xuri W25, GE Xuri W5, Sartorius BioSTAT RM 20
- the present invention relates to a composition for preventing hair loss or promoting hair growth
- a composition for preventing hair loss or promoting hair growth comprising as an active ingredient dermal papilla cells differentiated from adipose-derived stem cells, obtained according to the production method described above.
- the pharmaceutical composition of the present invention can be prepared as an oral or parenteral dosage form by a conventional method known in the art depending on the route of administration, including a pharmaceutically acceptable carrier or excipient.
- Such pharmaceutically acceptable carriers or excipients are those that do not inhibit the activity or properties of the drug without being particularly toxic to the human body, and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate, algae, etc. Nate, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water (e.g. saline and sterile water), syrup, methyl cellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc.
- a suitable carrier or excipient may be one of the following ingredients: saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, and ethanol.
- saline solution sterile water
- Ringer's solution buffered saline solution
- albumin injection solution dextrose solution
- maltodextrin solution glycerol
- ethanol ethanol
- the above ingredients can be used alone or in combination, and other common pharmaceutical additives such as antioxidants, buffers, and bacteriostatic agents can be added as needed.
- the pharmaceutical composition of the present invention when formulated for oral administration, it can be manufactured in the form of tablets, troches, capsules, elixirs, suspensions, syrups, wafers, etc., and when formulated for parenteral administration, especially as an injection, it can be manufactured in unit dosage ampoules or multiple doses. It can be prepared in single dosage form.
- the pharmaceutical composition of the present invention can be manufactured in the form of solutions, suspensions, tablets, pills, capsules, sustained-release preparations, etc.
- the pharmaceutical composition of the present invention is formulated into a unit dosage form suitable for administration into the patient's body according to a conventional method in the pharmaceutical field, and is administered through an oral administration route using an administration method commonly used in the art. or on the skin, intralesional, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intraventricular, pulmonary, transdermal, subcutaneous, intraperitoneal, intranasal, digestive tract, topical, sublingual, intravaginal, It can be administered by parenteral administration routes, such as the rectal route.
- the dosage (effective amount) of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, administration method, patient's age, weight, gender, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. It can be prescribed appropriately, and a person skilled in the art can appropriately determine the dosage by considering these factors.
- the pharmaceutical composition of the present invention is prepared as an injection in the form of a unit dose.
- the amount of hair follicle cells contained per unit dose of the pharmaceutical composition of the present invention is 10 2 -10. It may be in the range of 7 cells/ml.
- compositions for inducing differentiation of adipose-derived stem cells into dermal papilla cells a method for differentiating dermal papilla cells using the composition, and a pharmaceutical composition for preventing hair loss or promoting hair growth.
- composition and differentiation method for inducing differentiation of the present invention are techniques for differentiating dermal papilla cells from adipose-derived stem cells using moroniside, and these differentiated dermal papilla cells can have a useful effect as a cell therapy agent for hair loss treatment. there is.
- Figure 1 is a diagram showing the process of differentiating dermal papilla cells from human adipose-derived stem cells according to the present invention.
- Figure 2 shows the results of confirming the toxicity of the substance inducing differentiation into dermal papilla cells of the present invention in human adipose-derived stem cells.
- Figure 3 shows the results of confirming the expression level of genes of Versican, Corin, Bmp2, and Bmp4, which are essential factors for dermal papilla cells, after inducing differentiation from human adipose-derived stem cells into dermal papilla cells.
- Figure 4 shows the results of confirming the expression level of genes for Wnt5 ⁇ , Lef-1, Hey-1, and Wif-1, which are dermal papilla cell growth factors related to Wnt5 ⁇ , after inducing differentiation from human adipose-derived stem cells into dermal papilla cells.
- Figure 5 shows hair follicle formation by H&E staining of mouse tissues of the non-cell-administered control group (#1), human adipose-derived stem cell-administered group (#2), control dermal papilla cell-administered group (#3), and differentiated cell-administered group (#4). This is a photo showing the extent.
- Human adipose tissue used in the present invention was purchased from Goma Biotech Co., Ltd. (Seoul, Korea), and stem cells were isolated from adipose tissue by the method of Zuk et al. (Mol Biol Cell. 2022 Dec; 13(12): 4279-4295 ) was performed in accordance with.
- stem cells from adipose tissue After isolating stem cells from adipose tissue, they were cultured in DMEM (Dulbecco's Modified Eagle's Medium) supplemented with penicillin (100 U/ml), streptomycin (100 ug/ml), and 10% heat-inactivated serum in 95% air and 5% CO2. and cultured at 37°C. When the cells attached to the culture dish grew, they were collected using 0.25% trypsin/10 mM EDTA and maintained in DMEM supplemented with 10% (w/v) Fetal Bovine Serum (FBS).
- DMEM Dulbecco's Modified Eagle's Medium
- penicillin 100 U/ml
- streptomycin 100 ug/ml
- 10% heat-inactivated serum in 95% air and 5% CO2.
- human dermal papilla cells were purchased from PromoCell and used as a control (Dermal papilla cell, DPC).
- the culture method was one of culturing human adipose-derived stem cells. same.
- a differentiation inducing medium of a new composition was prepared to differentiate dermal papilla cells from human adipose-derived stem cells.
- the medium is a medium used for culturing human adipose-derived stem cells as in Example 1 (DMEM supplemented with 10% (w/v) FBS) and basic fiber as an active ingredient for inducing differentiation into dermal papilla cells. It was prepared by mixing 10 ng/ml of fibroblast growth factor-basic (bFGF), 1 ng/ml of bone morphogenetic protein 2 (BMP2), and 10 ⁇ M of morroniside.
- bFGF fibroblast growth factor-basic
- BMP2 bone morphogenetic protein 2
- the differentiation inducing composition prepared in this way is shown in Table 1 below, and was named FDI-1 (Frombio Differentiation Inducer-1) for convenience.
- FDI-1 Frombio Differentiation Inducer-1
- a differentiation induction medium containing 6BIO (6-bromo-indirubin-3'-oxime), which is known to be effective in the differentiation of existing dermal papilla cells, was used instead of moroniside as a control group.
- bFGF bFGF
- BMP2 BMP2, 6BIO, and Morroniside
- composition of differentiation inducing composition Composition type menstruum Added substance 1 Additive substance 2 Additive substance 3 Differentiation-inducing composition (FDI-1) DMEM (10% FBS) 10 ng/ml bFGF 1 ng/ml BMP2 10 ⁇ M Morroniside comparison group 10 ⁇ M 6BIO
- Example 3 Method of differentiating human adipose-derived stem cells into dermal papilla cells
- Human adipose-derived stem cells were inoculated into 6-well plates at a concentration of 1 ⁇ 10 5 cells/well, 1 ml each, and culture conditions used in Example 1 were used. and cultured for 24 hours. When the cells attached to the bottom, they were washed with the solvent DPBS (Dulbecco's Phosphate-buffered saline) and then treated with FDI-1 to induce differentiation.
- DPBS Dynamicon-phosphate-buffered saline
- CCK-8 a reagent used to confirm toxicity, was purchased from Dongin Biotech (Seoul, Korea), and human adipose-derived stem cells were used as cells isolated in Example 1 above.
- 100 ul of human adipose-derived stem cells were treated in 96-well plates at a concentration of 1 ⁇ 10 4 cells/well, and then cultured for 24 hours under the culture conditions used in Example 1.
- the cells attached to the bottom they were washed with DPBS, a solvent, and then treated with FDI-1 and cultured for up to 72 hours.
- culture was performed for 3 hours with 10 ul of CCK-8 reagent and 100 ul of human adipose-derived stem cell culture medium, and then the absorbance was measured with a spectrophotometer at 540 nm. did.
- Real-time PCR Real-time PCR was performed using the SYBR green method using the synthesized cDNA and primers for adipose-derived stem cell-specific marker genes in Table 1 below.
- SYBR Green I is an interchelator that binds to double-stranded DNA and exhibits fluorescence. Interchelator emits fluorescence by binding to double-stranded DNA synthesized through PCR reaction, and the amount of amplification product produced can be measured by detecting this fluorescence intensity.
- the expression level of the stem cell pluripotency marker gene was examined in the same manner.
- Wnt5 ⁇ -related dermal papilla cell growth genes Wnt5 ⁇ , Lef-1, Hey-1, and Wif-1 were confirmed using real-time PCR, and the primer sequences for each factor are shown in Table 3 below.
- the expression of Wnt5 ⁇ -related dermal papilla cell growth factor was very high in cells that induced differentiation by treatment with a comparative composition containing FDI-1 and 6BIO.
- the expression of Wnt5 ⁇ -related dermal papilla cell growth factor is similar or higher in the group treated with FDI-1, the differentiation induction medium of the present invention, compared to the group treated with the control differentiation induction medium.
- Animal testing model hair growth efficacy test division cell type Number of doses Dosage administered Method of administration observation period #One Negative control group Non-administration 1 dose 1 Transdermal administration 4 weeks (30 days) #2 Positive control group 1 Human adipose-derived stem cells #3 Positive control group 2 hair papilla cells #4 test group FDI-1 differentiated cells
- the formation of hair follicles occurred at a very high frequency in the group administered cells (#4) induced differentiation with FDI-1 compared to the group not administered cells, which was the negative control group (see arrow).
- the hair follicles in the differentiated cell-administered group (#4) were larger in diameter and longer than the human adipose-derived stem cell-administered group (#2), which was used as a positive control group.
- the hair follicle formation rate and the size and length of hair follicle diameter were similar in the differentiated cell administration group (#4), indicating that cells differentiated from human adipose-derived stem cells according to the present invention were It can be seen that it has a similar function to dermal papilla cells.
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Abstract
L'invention concerne une composition pour induire la différenciation de cellules souches issues du tissu adipeux en cellules de papille dermique, et un procédé de différenciation utilisant la composition. La composition pour induire la différenciation et le procédé de différenciation, selon la présente invention, se rapportent à des technologies utilisant du morroniside pour permettre à des cellules de papille dermique d'être différenciées à partir de cellules souches issues du tissu adipeux, et les cellules de papille dermique différenciées peuvent être utiles en tant qu'agent thérapeutique cellulaire pour le traitement de la perte des cheveux.
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KR20180137781A (ko) * | 2017-06-19 | 2018-12-28 | 연세대학교 산학협력단 | 지방유래줄기세포로부터 모유두 세포로의 분화방법 및 이의 용도 |
WO2019017691A2 (fr) * | 2017-07-19 | 2019-01-24 | 서울대학교 산학협력단 | Procédé de différenciation de cellule souche pluripotente induite humaine en cellule précurseur de papille dermique et son utilisation |
KR102141641B1 (ko) * | 2020-01-31 | 2020-08-06 | 주식회사 래디안 | 인간지방 유래 중간엽 줄기세포로부터 모유두세포로의 분화방법 |
KR102543431B1 (ko) * | 2022-10-05 | 2023-06-15 | 주식회사 프롬바이오 | 지방 유래 줄기세포의 모유두세포로의 분화 유도용 조성물 및 그 조성물을 이용한 분화 방법 |
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Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20180137781A (ko) * | 2017-06-19 | 2018-12-28 | 연세대학교 산학협력단 | 지방유래줄기세포로부터 모유두 세포로의 분화방법 및 이의 용도 |
WO2019017691A2 (fr) * | 2017-07-19 | 2019-01-24 | 서울대학교 산학협력단 | Procédé de différenciation de cellule souche pluripotente induite humaine en cellule précurseur de papille dermique et son utilisation |
KR102141641B1 (ko) * | 2020-01-31 | 2020-08-06 | 주식회사 래디안 | 인간지방 유래 중간엽 줄기세포로부터 모유두세포로의 분화방법 |
KR102543431B1 (ko) * | 2022-10-05 | 2023-06-15 | 주식회사 프롬바이오 | 지방 유래 줄기세포의 모유두세포로의 분화 유도용 조성물 및 그 조성물을 이용한 분화 방법 |
Non-Patent Citations (1)
Title |
---|
LIJUAN ZHOU, HAN WANG, JING JING, LIJUAN YU, XIANJIE WU, ZHONGFA LU: "Morroniside regulates hair growth and cycle transition via activation of the Wnt/β-catenin signaling pathway", SCIENTIFIC REPORTS, vol. 8, no. 1, 1 December 2018 (2018-12-01), XP055746412, DOI: 10.1038/s41598-018-32138-2 * |
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